Cockcroft-Gault Equation Research Articles

Novel formula using triceps skinfold thickness to revise the Cockcroft-Gault equation for estimating renal function in Japanese bedridden elderly patients.

In recumbent elderly patients, creatinine clearance (eCCr) estimated by the Cockcroft-Gault (CG) equation may not necessarily reflect renal function. We aimed to develop a novel formula to revise the CG equation using anthropometric measurements in bedridden elderly patients and evaluate its clinical utility. The subjects included 77 bedridden Japanese patients aged ≦ 65, hospitalized at Naruto Yamakami Hospital. The actual CCr (mCCr) value was measured using the 24-hour urine collection method. Anthropometric data, such as skeletal muscle mass, body fat mass (BFM), and triceps skinfold thickness (TSF), were collected. We established a novel formula to estimate CCr(BFM) or CCr(TSF) by correcting the eCCr(Enz+0.2) value with BFM or TSF. The stage of classification of renal dysfunctions in patients with eGFR(BFM) or eGFR(TSF) was equivalent to the GFR(control) based on the mCCr. Notably, the novel equation for eCCr based on TSF (eCCr(TSF)), dubbed the "Naruto" formula, can be useful to evaluate renal function in bedridden elderly patients without expensive equipment or additional costs. In this study, mCCr was considered to be the true renal function of the patient, but whether and to what extent mCCr correlates with inulin clearance is unknown. J. Med. Invest. 65:195-202, August, 2018.

Estimating Renal Function in the Elderly Malaysian Patients Attending Medical Outpatient Clinic: A Comparison between Creatinine Based and Cystatin-C Based Equations.

Background To assess the performance of different GFR estimating equations, test the diagnostic value of serum cystatin-C, and compare the applicability of cystatin-C based equation with serum creatinine based equation for estimating GFR (eGFR) in comparison with measured GFR in the elderly Malaysian patients. Methods A cross-sectional study recruiting volunteered patients 65 years and older attending medical outpatient clinic. 51 chromium EDTA (51Cr-EDTA) was used as measured GFR. The predictive capabilities of Cockcroft-Gault equation corrected for body surface area (CGBSA), four-variable Modification of Diet in Renal Disease (4-MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using serum creatinine (CKD-EPIcr) as well as serum cystatin-C (CKD-EPIcys) were calculated. Results A total of 40 patients, 77.5% male, with mean measured GFR 41.2 ± 18.9 ml/min/1.73 m2 were enrolled. Mean bias was the smallest for 4-MDRD; meanwhile, CKD-EPIcr had the highest precision and accuracy with lower limit of agreement among other equations. CKD-EPIcys equation did not show any improvement in GFR estimation in comparison to CKD-EPIcr and MDRD. Conclusion The CKD-EPIcr formula appears to be more accurate and correlates better with measured GFR in this cohort of elderly patients.

Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations for estimating glomerular filtration rates in cancer patients receiving cisplatin-based chemotherapy.

BackgroundAlthough the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has been recommended for accurate estimates of glomerular filtration rate (eGFR), there is little information regarding differences in GFR estimates obtained using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations in East Asian cancer patients. We investigated discrepancies in GFR and toxicities in patients treated with cisplatin-based chemotherapy using three equations equations.MethodsA total of 229 patients were retrospectively recruited. We calculated eGFR using the three equations and separated patients into three categories based on GFR < 10 (group A), 10–50 (group B), and > 50 (group C) mL/min/1.73m2. We analyzed chemotherapy toxicities.ResultsThe mean eGFR calculated using the CG was the lowest of the values derived using the three equations. Estimates using the MDRD and CKD-EPI equations resulted in reclassifying 32 (71.1%) and 33 (73.3%) of 45 patients, originally placed in group B using the CG into group C. However, only 1 (7.7%) of 13 patients placed in group B using the MDRD were reclassified into group C using the CKD-EPI. Twenty-eight of 45 patients classified into group B using the CG equation were treated with reduced doses of cisplatin. However, these patients did not show significant differences in toxicities compared with other patients taking full doses of cisplatin.ConclusionThe CG equations underestimated GFR compared to the MDRD and CKD-EPI equations. Therefore, when GFR is estimated using CG equations, East Asian cancer patients may receive insufficient doses of chemotherapeutic agents, including cisplatin.

Population pharmacokinetics of teicoplanin in hospitalized elderly patients using cystatin C as an indicator of renal function

Serum cystatin C (CysC) has recently been proposed as an alternative marker to serum creatinine (SCR) for estimating renal clearance. In the present study, we performed a population pharmacokinetic analysis of teicoplanin (TEIC), which is mainly eliminated through the kidneys, using CysC as a predictor for renal clearance. Thirty-six patients with MRSA infections who were administrated to the National Hospital Organization Beppu Medical Center between January 2012 and December 2013 were enrolled and gave 123 sets of blood TEIC concentration data. Renal clearance was estimated by the Hoek equation using CysC, by creatinine clearance predicted by the Cockcroft-Gault equation using SCR, or directly by CysC. One compartment open model with inter-individual variabilities for renal clearance and the volume of distribution as well as an additional residual error model was used to estimate population pharmacokinetic parameters for TEIC. The model with the best predictability was that with CysC as a predictor for renal clearance; it showed better significance than the models using estimated the glomerular filtration rate by the Hoek equation or CLcr. The final model was as follows: CL (L/hr)=0.510×(CysC/1.4)-0.68×Total body weight/600.81, omega (CL)=19.8% CV, VC (L)=78.1, omega (V)=42.7% CV. The present results show the usefulness of CysC to more accurately predict the pharmacokinetics of drugs mainly eliminated through the kidneys, such as TEIC. However, since the sample size in this study was relatively small, further investigations on renal clearance predictability using CysC are needed.

Discrepancies between the use of MDRD-4 IDMS and CKD-EPI equations, instead of the Cockcroft–Gault equation, in the determination of the dosage of direct oral anticoagulants in patients with non-valvular atrial fibrillation

Background and objectiveDirect oral anticoagulants (DOACs) require dose adjustment according to estimated clearance creatinine (eClCr) using the Cockcroft–Gault (CG) equation. There are discrepancies with the equations that estimate glomerular filtration rate (eGFR). We analyse how the use of the CKD-EPI and MDRD-4 IDMS equations affect the recommended dosage for ACODs. Patients and methodsRetrospective study of patients with non-valvular atrial fibrillation seen at a cardiology clinic between November 2012 and August 2014. Patients were reclassified according to the recommended dosage for dabigatran, rivaroxaban, apixaban and edoxaban, based on the eGFR equation used. Other clinical factors are taken into account, according to the product label. We analysed the percentage of discordance. ResultsFour hundred and fifty-four patients, 53.3% men, with a mean age of 68.7±13.8 years were studied. The mean intra-individual differences recorded for the CG equation were 3.9ml/min/1.73m2 with MDRD-4 IDMS (95% CI 1.4–6.4, p=0.003) and 11.3ml/min/1.73m2 with CKD-EPI (95% CI 8.9–13.7, p<0.001). A gradient is observed in the discordance of the posology (apixaban 1.1%, dabigatran 3.5%, edoxaban 5.7%, rivaroxaban 8.4% with MDRD-4 IDMS). Differences were limited to patients with eClCr<60ml/min and were more evident in ≥75 years in which the eGFR equations overestimate renal function. ConclusionsIn patients with non-valvular atrial fibrillation, especially with renal failure and in the elderly, eGFR equations tend to overestimate renal function relative to CG and therefore suggest an overdose of DOACs.

Reduced estimated glomerular filtration rate is associated with depressive symptoms in elder Chinese: A population-based cross-sectional study

Depression has been associated with chronic kidney disease (CKD). However, few studies have examined whether such association exist in average older individuals with mild to moderate reduced kidney function. This study investigated the association between reduced estimated glomerular filtration rate (eGFR) and depressive symptoms in Chinese older population. Data was obtained from the Rugao Longevity and Ageing Study conducted in Jiangsu, China. Cockcroft-Gault (CG) equation was used to calculate eGFR. Depressive symptoms were defined by using Chinese version of 15-item Geriatric Depression Scale (GDS-15). The prevalence of depressive symptoms was 9.9% among 1749 elderly participants aged 70–84 years. Many elderly had a mild to moderate reduced renal function (84.3%, 57.1% in stage2 CKD and 27.2% in stage3 CKD, respectively). The overall GDS-15 score showed an upward trend with decreasing of eGFR (p < 0.05). Furthermore, a moderate decline of eGFR (in stage3 CKD) was significantly associated with increased risk of depressive symptoms even after adjusting for confounders (OR = 1.71, 95%CI 1.05–2.77, P = 0.03). Elder had no depressive symptoms if their eGFR was normal or mildly reduced. Our results suggest that a moderate decrease of eGFR (stage3 CKD) was independently associated with depressive symptoms in general Chinese elderly.

Concordance between modification of diet in renal disease, chronic kidney disease epidemiology collaboration and Cockcroft-Gault equations in patients with chronic kidney disease at St. Paul\u2019s hospital millennium medical college, Addis Ababa, Ethiopia

BackgroundThe most commonly used glomerular filtration rate estimating equations for drug dosing are Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. However there is still a concern about whether to use MDRD and CKD-EPI interchangeably with CG for drug dosage adjustment.MethodsThe study was initiated to determine the concordance between MDRD, CKD-EPI and CG equations and associated factors in patients with chronic kidney disease at Saint Paul’s Hospital Millennium Medical College (SPHMMC). This was a cross sectional study which involved patient chart review and physicians self-administered questionnaire. Serum creatinine level ≥ 1.2 mg/dL was used as a cutoff point in pre-selection of patients. The correctness of the drug dose prescribed for the level of renal function were compared to the drug database (Lexi-Comp) available through Up-to-date version 21.2.ResultsAmong the total of 422 patients, 249 (59%) were males. Mean age of patients was 46.09 years. The use of MDRD equation for drug dose adjustment by physicians working in the renal clinic of SPHMMC was six out of nine physicians. The Pearson correlation coefficient between the CG with MDRD and CKD-EPI equations was r = 0.94, P < 0.001 and r = 0.95, P < 0.001, respectively. The concordance between the CG with MDRD and CKD-EPI equations for FDA assigned kidney function categories was 73.7%, Kappa = 0.644 and 74.9%, Kappa = 0.659, respectively. Concordance between the CG with MDRD and CKD-EPI equations for the drug dosing recommendation was 89.6%, kappa = 0.782 and 92%, kappa = 0.834, respectively. Age > 70 years was associated with discordance between CG and MDRD equations for drug dosing recommendation whereas serum creatinine 1.2–3.5 mg/dL, weight < 61 Kg and age > 70 years were associated with discordance between the CG with MDRD and CKD-EPI equations for FDA assigned kidney function categories. However, none of the factors associated with discordance between CG and CKD-EPI for drug dosing.ConclusionMDRD equation can be used interchangeably with CG equation for drug dosing recommended in all adult patients between the age of 18 and 70 years. CKD-EPI can be used interchangeably with CG in all adult Ethiopian patients with CKD.

Monitoring the estimated glomerular filtration rate (eGFR) in patients with small-cell lung cancer during chemotherapy: equations based on serum creatinine or cystatin C?

This study compared the differences between the estimated glomerular filtration rate (eGFR) calculated by several equations based on serum creatinine (Scr) and cystatin C (CysC) concentrations for monitoring renal function in patients with small-cell lung cancer (SCLC) during chemotherapy. Seventy-one patients with SCLC were retrospectively analyzed. The eGFR before and after each chemotherapy cycle was calculated by the following equations: the chronic kidney disease epidemiology collaboration (CKD-EPI) equation, the modification of diet in renal disease (MDRD) equation, the Cockcroft-Gault (CG) equation, and five CysC-based equations. The patients were compared among the different eGFR groups. The mean decreases in eGFRCKD-EPI (-2.25±9.89ml/min/1.73m2) between each treatment cycle were more significant than the decreases in eGFRCG (-0.46±10.17ml/min/1.73m2), eGFRMDRD (-0.48±9.79ml/min/1.73m2), and five calculated eGFRCysC (p<0.05). Single-/multiparameter analyses showed that patients with a higher body mass index (BMI>23) and receiving more treatment cycles (>3) were at increased risk for developing renal impairment with an eGFR less than 60ml/min/1.73m2 during chemotherapy. The eGFR calculated by the CKD-EPI equation changed more significantly between each chemotherapy cycle than did the eGFR from the other equations based on Scr or CysC in patients with SCLC. Oncologists should pay more attention to the renal function of specific patient groups during treatment.

Characterization of variables for potential impact on vancomycin pharmacokinetics in thermal or inhalation injury

ObjectiveTo characterize the pharmacokinetics of vancomycin dosing in thermal or inhalation injury as they relate to percent total body surface area burn (TBSA) and days since injury (DSI). MethodsThis retrospective 3-year study included patients with thermal or inhalation injury receiving vancomycin. Patient demographics and course data were collected using the institution’s electronic medical record. ResultsSix hundred and fifty-four patients were included in the study; 124 remained after exclusion. Clearance (CL) was augmented in patients closer to their date of injury. CL and total daily dose requirements significantly increased with larger percent TBSA injured that was independent of volume of distribution (Vd). Larger percent TBSA also predicted increased occurrence of renal injury prior to vancomycin initiation. A modified sample set was also analyzed to control for renal dysfunction. Creatinine clearance (CrCl) estimated via the Cockcroft-Gault equation significantly impacted CL and total daily dose. To obtain a goal trough of 15–20mg/L, the average patient in the modified sample with ≥10% TBSA required 64.7mg/kg/day (or 16.2mg/kg every 6hours). ConclusionsDSI, percent TBSA, and CrCl can be used to predict faster vancomycin CL and need for higher total daily doses. Augmented pharmacokinetics can occur as early as two days after injury and decrease with time. Acceptable target trough attainment is still lacking and this data should assist in performance improvements for initial vancomycin dosing.

Renal manifestations of HIV during the antiretroviral era in South Africa: a systematic scoping review

BackgroundIt is estimated that 650,000 patients may develop human immunodeficiency virus (HIV)-related renal disease in South Africa. South Africa has recently adopted WHO policy, stipulating that all HIV-infected patients have access to antiretroviral treatment (ART) irrespective of CD4 cell count.MethodsWe searched Google Scholar, PubMed, Medline, Cochrane Library, Worldcat.org and EBSCO host databases from July 2015 to December 2015. Eligibility criteria included articles pertaining to renal manifestations of HIV in South Africa from 2004 to 2015 in adult patients (≥ 18 years). We independently reviewed the articles for quality. Thematic content analysis was performed to identify patterns of renal manifestations from the included studies. The risk of bias (e.g. internal validity) in the included studies was evaluated using the mixed methods appraisal tool.ResultsEleven out 21 studies were eligible for data extraction. The prevalence of urine abnormalities on urine dipsticks was high but had poor sensitivity and specificity for detecting renal impairment. Normal renal function occurred in 28.4 to 79% of patients, mild renal impairment occurred in 19 to 57.1% and moderate renal impairment in 2 to 14.4%. Severe renal impairment occurred in 1.3% of patients. Both the Cockcroft-Gault equation (after correcting for bias) and the 4-variable Modification of Diet in Renal Disease equation (without the ethnicity factor for African Americans) have been validated for the estimation of glomerular filtration rate (eGFR) in Black South Africans. HIV-associated nephropathy was the most prevalent histology seen (57.2%). Older age, a lower CD4 count, a low haemoglobin and a detectable viral load were associated with renal impairment. Renal function improved in the first year of commencing ART as evidenced by the regression of proteinuria and the increase in eGFR.ConclusionThe findings of the review have implications to the recently adopted ‘test and treat’ approach to HIV prevention and management.Systematic review registrationPROSPERO CRD42016039270

Evaluation of various equations for estimating renal function in elderly Chinese patients with type 2 diabetes mellitus.

BackgroundThe clinical assessment of kidney function based on the estimated glomerular filtration rate (GFR) in older patients remains controversial. This study evaluated the concordance and feasibility of using various creatinine-based equations for estimating GFR in elderly Chinese patients with type 2 diabetes mellitus (T2DM).MethodsA cross-sectional analytical study was conducted in 21,723 older diabetic patients (≥60 years) based on electronic health records (EHR) for Minhang District, Shanghai, China. The concordance of chronic kidney disease (CKD) classification among different creatinine-based equations was assessed based on Kappa values, intraclass correlation coefficient (ICC) statistics, and the eGFR agreement between the equations was tested using Bland–Altman plots. The GFR was estimated using the Cockcroft–Gault (CG), Berlin Initiative Study 1 (BIS1), simplified Modification of Diet in Renal Disease (MDRD), MDRD modified for Chinese populations (mMDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), CKD-EPI in Asians (CKD-EPI-Asia), and Ruijin equations.ResultsOverall, the proportion of CKD stages 3–5 (eGFR <60 mL/min/1.73 m2) was calculated as 28.9%, 39.1%, 11.8%, 8.4%, 14.3%, 11.5%, and 12.7% by the eGFRCG, eGFRBIS1, eGFRMDRD, eGFRmMDRD, eGFRCKD-EPI, eGFRCKD-EPI-Asia, and eGFRRuijin equations, respectively. The concordance of albuminuria and decreased eGFR based on the different equations was poor by both the Kappa (<0.2) and ICC (<0.4) statistics. The CKD-EPI-Asia equation resulted in excellent concordance with the CKD-EPI (ICC =0.931), MDRD (ICC =0.963), mMDRD (ICC =0.892), and Ruijin (ICC =0.956) equations for the classification of CKD stages, whereas the BIS1 equation exhibited good concordance with the CG equation (ICC =0.809). In addition, significant differences were observed for CKD stage 1 among all these equations.ConclusionAccurate GFR values are difficult to estimate using creatinine-based equations in older diabetic patients. Kidney function is complex, and the staff need to be aware of the individualized consideration of other risk factors or markers of reduced renal function in clinical practice.

Creation and Validation of a Pediatric Vancomycin Nomogram for a Goal Trough of 10–15 mg/L at a Quaternary Care Children’s Hospital

Abstract Background Recent data suggest a serum vancomycin (vanc) trough (VT) of 11mg/L correlates with an AUC/MIC24 &amp;gt; 400 which has shown to be the optimal concentration to eradicate MRSA infection and improve mortality. There are currently limited published recommendations on how to achieve such a VT in children. This study validates a vancomycin nomogram used to achieve a VT of 10–15 mg/L in pediatric inpatients (pts) at a quaternary care children’s hospital. Methods This is an 18 month (mo) prospective analysis beginning in September 2015. Included pts were ≥2 mo of age and had ≥2 consecutive VT. Pts receiving renal replacement therapy or those with a serum creatinine (Scr) of ≥0.5 mg/dL from a prior admission or within 48 hours of vanc initiation were excluded. The starting dose (SD) of vanc was determined by age and creatinine clearance (CrCl) (Tables 1 and 2). CrCl was measured by Bedside Schwartz equation for patients ≤18 years old (yo) and Cockcroft-Gault equation for patients &amp;gt;18 yo. The maximum CrCl was set to 120 ml/minute. Patients who were on vanc and experienced a Scr increase of ≥0.5 mg/dL were considered to have acute kidney injury (AKI). The study had a 6 mo evaluation period which led to a revised version (RVN) on March 2016. The primary endpoint (PE) was achievement of 10–15 mg/L by the Second VT for patients with the First trough outside of this range, using our RVN (Table 3). Results Overall, a total of 276 patients received vanc, 17 and 29 patients were dosed according to the initial and RVN, respectively. For young children (Table 1), the SD for patients with a CrCL ≥90 ml/minute was therapeutic, sub-, and supra-therapeutic in 43.75%, 47.5% and 8.75%, respectively. For older children (Table 2), the SD for patients with a CrCl ≥100 ml/minute was therapeutic, sub-, and supra-therapeutic in 41.1%, 35.7% and 23.2%, respectively. The initial VN was successful 12/17 (70.6%) in achieving the PE. Success in achieving the PE after the RVN was 26/29 (89.7%). In the RVN group, the most common initial troughs were 5–7 mg/L (33.3%), followed by &amp;gt;18 mg/L (27.6%). The mean VT using the RVN was 13.7 mg/L. The overall AKI incidence throughout the study was 3.2% (9/276) and 0% using the RVN. Conclusion Our RVN led to a Second VT within a target range of 10–15 mg/L for 89.7% of patients, allowing for more accurate and safer use of vancomycin in our institution. Disclosures All authors: No reported disclosures.

Estimates of Glomerular Filtration Rate by the Chronic Kidney Disease Epidemiology Collaboration Equations Best Correlates with Kinetic Estimates of Glomerular Filtration Rates in the Critically Ill

Introduction: Kinetic estimate of GFR (keGFR) is a more accurate estimate of GFR in the acute settings with rapidly changing kidney functions. It takes into account the changes of creatinine over time, creatinine production rate, and the volume of distribution, however needs serial measurement of creatinine. We evaluated which methods of the conventional eGFR measurement best correlates with keGFR. This could assist clinicians in using a simpler method of calculation and is useful in the absence of serial plasma creatinine. Materials and method: This is a secondary analysis of prospective observational study. Inclusion criteria includes age more than 18 years old, and exclusion criteria includes ICU admission of less than 48 hours, post elective surgery, and ICU readmission. Plasma creatinine were measured daily for five days, and eGFR were calculated using the Cockcroft-Gault, MDRD, CKD-EPI and keGFR equations. Results: One hundred and forty three patients were analysed, of which 78(54.5%) had AKI. keGFR strongly correlated with eGFRCKD-EPI at all time points (all r≥0.90, p&lt;0.0001). The correlation persisted in both AKI and No AKI patients. keGFR only correlated well with eGFRMDRD and eGFRCG in AKI patients but less in patients without AKI. Bland Altman analysis showed that eGFRMDRD had the least bias, but eGFRCKD-EPI had the greatest precision. Conclusion: The new equation, keGFR strongly correlated with the eGFR by the CKD-EPI equation regardless of the time points and AKI status, and had the greatest precision. In the absence of serial plasma creatinine measurement, eGFR can accurately be estimated by the CKD-EPI equation compared to others.

Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy.

BackgroundPregnancy increases the risk of morbidity and mortality in sickle cell disease. We previously showed pregnant women with sickle cell disease to have a relatively low plasma renin concentration in late pregnancy, associated with a lack of the expected plasma volume expansion. We hypothesized this to be due to increased systemic vascular resistance through an imbalance between the vasodilator prostacyclin and vasoconstrictor thromboxane, associated with decreased glomerular filtration rate (GFR).ObjectiveTo compare estimated prostacyclin, thromboxane and GFR in non-pregnant and pregnant women with hemoglobin SS (HbSS) and AA (HbAA).Study designFour groups of 20 normotensive, nulliparous women were studied in Lagos, Nigeria: pregnant HbSS or HbAA women at 36–40 weeks gestation; non-pregnant HbSS and HbAA controls. We measured stable metabolites of prostacyclin and thromboxane A2 by enzyme-linked immunosorbent assay; GFR using the Cockcroft-Gault equation. Data analysis was by independent (Student’s) t-test or Mann-Whitney U test for comparisons between any two groups of continuous variables, univariate ANOVA for multiple groups and Pearson’s correlation coefficient for degree of association between variables.ResultsHbSS women had lower serum 6-keto-PGF1α concentrations than HbAA, whether pregnant or non-pregnant (P<0.001; P<0.004 respectively). Conversely, pregnant HbSS women had higher serum TxB2 (P<0.001); non-pregnant HbSS women had non-significantly higher TxB2 concentrations. The 6-keto-PGF1α:TxB2 ratio was markedly increased (pro-vasodilatory) in HbAA pregnancy (P<0.001) but reduced in HbSS pregnancy (P = 0.037). GFRs (mL/min) were higher in non-pregnant HbSS than HbAA (P<0.008) but only marginally raised in HbSS women in late pregnancy (P = 0.019) while markedly raised in HbAA pregnancy (P<0.001).ConclusionThe lower ratio of prostacyclin-thromboxane metabolites in HbSS pregnancy may indicate endothelial damage and an increased tendency to vasoconstriction and clotting. If confirmed by subsequent longitudinal studies, interventions to increase prostacyclin and reduce thromboxane, such as low dose aspirin, may be potentially useful in their management.

Refining the Policy for Timing of Kidney Transplant Waitlist Qualification.

Earlier qualification for the kidney transplant waitlist expedites transplant and is therefore associated with improved outcomes. U.S. Organ Procurement and Transplantation Network policies state that "measured or calculated creatinine clearance or glomerular filtration rate less than or equal to 20 mL/min" triggers waitlist time accrual. The choice of qualification method is somewhat arbitrary, and the policy implies that decline in renal function is monotonic. (1) We used survival analysis to quantify temporal differences in waitlist qualification by applying 3 kidney-function-estimating equations (Cockcroft-Gault, Modification of Diet in Renal Disease study, Chronic Kidney Disease Epidemiology Collaboration) to serial creatinine measurements from 3 patient cohorts: 1 of waitlisted patients at a major U.S. academic center and 2 national, multicenter cohorts of chronic kidney disease patients (African American Study of Kidney Disease and Hypertension, Modification of Diet in Renal Disease). (2) Survival analysis assessed whether requiring patients to demonstrate persistently reduced renal function on 2 occasions at least 90 days apart would meaningfully change qualification order. On average, time to waitlist qualification would be delayed on the order of 1 to 2 years by using calculated creatinine clearance (per the Cockcroft-Gault equation). Compared with current policy, requiring demonstration of persistently reduced renal function delayed qualification by 0.6 to 2.1 years and caused 40% to 50% of patients to switch the order in which they qualify by 6 months or more. The kidney transplantation policies should be revised, such that timing of waitlist qualification is more standardized. We suggest that mention of using calculated creatinine clearance be dropped from the Organ Procurement and Transplantation Network policy wording and the units to quantify kidney function be changed to mL/min per 1.73 m2. Some consideration should be given to whether requiring persistently reduced renal function would better identify patients most likely to benefit from earlier waitlist qualification.

Discrepancias entre el empleo de las ecuaciones MDRD-4 IDMS y CKD-EPI en vez de la de Cockcroft-Gault en la determinación de la posología de los anticoagulantes orales directos en pacientes con fibrilación auricular no valvular

Background and objectiveDirect oral anticoagulants (DOACs) require dose adjustment according to estimated clearance creatinine (eClCr) using the Cockcroft-Gault (CG) equation. There are discrepancies with the equations that estimate glomerular filtration rate (eGFR). We analyse how the use of the CKD-EPI and MDRD-4 IDMS equations affect the recommended dosage for ACODs. Patients and methodsRetrospective study of patients with non-valvular atrial fibrillation seen at a cardiology clinic between November 2012 and August 2014. Patients were reclassified according to the recommended dosage for dabigatran, rivaroxaban, apixaban and edoxaban, based on the eGFR equation used. Other clinical factors are taken into account, according to the product label. We analysed the percentage of discordance. ResultsFour hundred and fifty-four patients, 53.3% men, with a mean age of 68.7±13.8 years were studied. The mean intra-individual differences recorded for the CG equation were 3.9ml/min/1.73m2 with MDRD-4 IDMS (95% CI 1.4-6.4, P=.003) and 11.3ml/min/1.73m2 with CKD-EPI (95% CI 8.9-13.7, P<.001). A gradient is observed in the discordance of the posology (apixaban 1.1%, dabigatran 3.5%, edoxaban 5.7%, rivaroxaban 8.4% with MDRD-4 IDMS). Differences were limited to patients with eClCr<60ml/min and were more evident in≥75 years in which the eGFR equations overestimate renal function. ConclusionsIn patients with non-valvular atrial fibrillation, especially with renal failure and in the elderly, eGFR equations tend to overestimate renal function relative to CG and therefore suggest an overdose of DOACs.

Comparison of MDRD, CKD-EPI, and Cockcroft-Gault equation in relation to measured glomerular filtration rate among a large cohort with diabetes

AimsTo analyze the performance of Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft-Gault (CG), and CG calculated with ideal bodyweight (CG-IBW) equations to estimate glomerular filtration rate (eGFR) based on serum creatinine in a large diabetic population. Methods24,516 adults with type-1-diabetes or type-2-diabetes from the multicenter diabetes prospective follow-up registry DPV were analyzed. We compared eGFR and measured GFR (mGFR) based on 24-h urine collection by calculating mean bias (difference), precision (SD of this difference), accuracy (proportion of eGFR within ±10% of mGFR), Bland-Altman-plots. ResultsCG overestimates, whereas MDRD, CKD-EPI, and CG-IBW underestimate. Smallest mean bias and highest accuracy (75.3%) were observed for MDRD compared to the other equations (p<0.0001). MDRD and CKD-EPI estimated most accurately in stages 1 (MDRD:57.7%, CKD-EPI:57.3%) and 2 (MDRD:80.2%, CKD-EPI:80.7%). In stages 3 to 5, highest accuracy was observed for the MDRD (stage 3:82.3%, stage 4:77.8%, stage 5:71.0%). Among younger subjects, accuracy was higher using the CKD-EPI (18–<40years:63.7%, 40–<60years:72.8%). Above age 60years, MDRD estimated most accurately (60–<70years:77.3%, ≥70years:78.8%). In males and females, MDRD estimated most accurately (males:75.3%, females:75.3%). ConclusionIn this large diabetic cohort, smallest bias and highest accuracy were observed for the MDRD.

Role of dry lean body mass for estimation of glomerular filtration rate in kidney transplant recipients.

The use of equations that predict glomerular filtration rate (GFR) in patients with a kidney graft is still a matter of debate. The purpose of this study was to determine the level of accuracy of GFR equations and the relevance of dry lean body mass in the assessment of GFR. In a prospective clinical study, 100patients with a kidney graft were included. Estimated GFR with Modification of Diet in Renal Disease equation (MDRD), Chronic Kidney Disease Epidemiology Collaboration equation (CKD EPI) with serum creatinine concentration (CKD EPI Cr), serum cystatin C concentration (CKD EPI CysC) or both (CKD EPI Cr-CysC), and creatinine clearance calculated with Cockcroft-Gault equation (CG) was compared with GFR measured by 51Cr-EDTA clearance (mGFR 51Cr-EDTA). Dry lean body mass (body mass without fat mass and body water) was measured with bioimpedance analysis. All of the estimating equations overestimated mGFR 51Cr-EDTA by a significant degree (bias±SD in mL/min/1.73m2, 30% accuracy in brackets): CG 16.8±14.1 (44%), MDRD 12.5±15.3 (54%), CKD EPI Cr 15.1±15.3 (50%), CKD EPI CysC 8.0 ± 16.6 (56%), CKD EPI Cr-CysC 10.3 ± 13.4 (55%). Dry lean body mass significantly correlated with mGFR 51Cr-EDTA, but not with estimated GFRs. The estimating GFR equations are neither accurate nor precise in renal transplant recipients. Dry lean body mass is an important parameter that could potentially improve the GFR estimation in this population. .

Renal function estimations and dose recommendations for Gabapentin, Ibuprofen and Morphine in acute hip fracture patients

Abstract Aims Optimization of pain management is essential for fasttrack surgery and safety in acute hip fracture (AHF) patients. Kidney function determines the doses of several postoperative painkillers, but previous studies have shown the standard Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation overestimate glomerular filtration rate (GFR) in elderly and underweight patients. The optimized Cockcroft Gault (CGop) equation might be more accurate in this patient group. The study aims to (1) investigate the differences in estimated GFR (eGFR) based on CKD-EPI and CGop and (2) to simulate this impact on recommended dosing of standard painkillers in AHF patients. Methods Patients admitted with AHF from January to April 2015 were included. eGFR was calculated for each patient by CKD-EPI and CGop based on the lowest measured serum creatinine between 1 and 4 days postoperatively. CKD-classification (1–5) was performed based on both eGFR values. If patients were classified differently based on the two eGFR values, then drug dosages were simulated for Morphine, Ibuprofen and Gabapentin according to prescribing recommendations in Renbase®.Two-sided Mann–Whitney test was used to compare median values between groups. Results 176 patients (62% women) with a median age of 76 years were included. CKD-EPI (78.0mL/min/m2) estimated eGFR significantly higher compared with GGop (58.9, P &lt; 0.001). Depending on the equation used to estimate GFR, CKD ≥ 3 (eGFR &lt; 60 mL/min/m2) occurred in 23–53% all patients. Using CGop to estimate GFR resulted in CKD re-classification for 63% of all patients. Using CKD-EPI to estimate GFR resulted in significantly higher doses of Morphine, Ibuprofen and Gabapentin (P &lt; 0.0001) in re-classified patients. Conclusions GFR estimates are significantly higher when calculated by CKD-EPI compared to CGop, and this difference results in significantly higher recommended doses of painkillers in AHF patients. Future studies should include a gold standard for measuring GFR and maybe alternative biomarkers for the renal function.

Assessment of Glomerular Filtration Rate in Health and Disease: A State of the Art Review.

Acute and chronic kidney diseases affect pharmacokinetics and pharmacodynamics. There has been substantial progress in the past 20 years in the use of glomerular filtration rate (GFR) estimating equations. In principle, use of a single equation for each filtration marker (creatinine, cystatin C, or the combination) for detection, evaluation, and management of kidney disease and for drug development and dosing would facilitate clinical practice. We review the principles for assessment of GFR, provide historical perspectives and updates regarding use of GFR estimating equations, including assay methods for filtration markers, performance of estimating equations, and recommendations by clinical practice guideline groups and regulatory agencies. We conclude that it is time to change from rigid adherence to the use of the Cockcroft-Gault equation for use in drug development and drug dosing to the more accurate and more widely used Modification of Diet in Renal Disease (MDRD) study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.